1. Field of the Invention
The present invention relates to a fluid dispenser for fluid in assay. More particularly, the present invention relates to a fluid dispenser for fluid in assay, in which pipette devices can be moved up and down selectively even with a simple structure of a pipette head.
2. Description Related to the Prior Art
An assay apparatus for assay in utilizing attenuated total reflection is used for various kinds of studies in a biochemical field or the like, for example to study interaction of protein, DNA and various biomaterials, and to select candidate drugs by screening. Also, the technique is useful in the fields of the clinical medicine, food industries and the like.
A surface plasmon resonance (SPR) sensor is known as an assay apparatus for assay in utilizing attenuated total reflection. A thin film/dielectric interface of a metal film is fitted on a dielectric block. Light is directed to the thin film/dielectric interface in a manner conditioned for total reflection. Surface plasmon is a term to mean the compressional wave created on the surface of the metal and included in plasmon as quantized expression of the compressional wave. Free electrons in a metal vibrate to generate the compressional wave.
In the assay apparatus, the sensing surface is positioned opposite to the interface where the metal thin film is connected with the dielectric block. The sensing surface is caused to create surface plasmon resonance. Reaction of samples is assayed by detecting the SPR on the sensing surface.
Illuminating light is applied to an interface between the thin film and the prism or a surface back to the sensing surface at an angle of incidence equal to or more than a critical angle to satisfy a condition of total reflection. Then total reflection of the illuminating light occurs. Upon the total reflection created on the metal/dielectric interface, a small component of the light passes through the metal film without reflection, and penetrates to the sensing surface. A wave of the penetrating component is called an evanescent wave. Surface plasmon resonance (SPR) is created when frequency of the evanescent wave coincides with that of the surface plasmon. In response to this, intensity of the reflected light attenuates remarkably. In the assay apparatus, the attenuation in the reflected light reflected by the metal/dielectric interface is detected, to recognize creation of the SPR on the sensing surface.
A resonance angle or an angle of incidence of light for creation of surface plasmon resonance depends upon a refractive index of a medium of transmission of evanescent waves and surface plasmon. In other words, a change in the refractive index of the medium of transmission causes a change in the resonance angle of creation of SPR. The substance or sample in contact with the sensing surface is the medium for transmitting the evanescent waves and surface plasmon. When binding, dissociation or other reaction occurs on the sensing surface between two molecules or samples, the resonance angle changes because of a change in the refractive index of the medium of transmission. The SPR assay apparatus finds the changes in the resonance angle, to assay the interaction between the molecules or samples.
An assay apparatus for assay in utilizing attenuated total reflection is used for various kinds of studies in a biochemical field or the like, for example to study interaction of protein, DNA and various biomaterials, and to select candidate drugs by screening. Also, the technique is useful in the fields of the clinical medicine, food industries and the like. A sample or biomaterial, such as protein, is handled as sample fluid.
JP-A 6-167443 discloses an SPR assay apparatus in which an optical system of Kretschmann configuration is used for incidence of light to the metal film. According to the Kretschmann configuration, the thin film/dielectric interface of the metal film is fitted on a prism, which condenses light and directs the light to the thin film/dielectric interface in a manner conditioned for total reflection. A sensing surface is overlaid inside the flow channel, for immobilizing the sample. A flow channel is disposed so that the sensing surface lies therein. Ligand fluid is introduced to the flow channel for immobilizing the ligand on the sensing surface. After this, analyte fluid is introduced for contact of the analyte and the ligand, to assay the interaction between those.
For assay, at first liquid buffer is introduced to a flow channel and flows on to a sensing surface. Then measurement of an output signal is started. After this, analyte fluid is introduced. The liquid buffer in the flow channel is caused by the analyte fluid to flow out and exit from an orifice of the flow channel. The analyte fluid is kept stored in the flow channel, before the liquid buffer is introduced to terminate the measurement of the signal. It is possible to detect a baseline of the signal and detect a signal in the period including step of interaction between analyte and ligand, and their dissociation.
To introduce the analyte fluid to the sensing surface, a fluid dispenser including a pipette device is used. The pipette device is useful because of easy loading and unloading to an orifice of the flow channel in view of rapid assay for a great number of sensor units in a large scale.
The flow channel has a U shape as viewed in a section, and two end orifices open in an upper surface. The fluid dispenser has two of the pipette devices disposed at a pitch of the orifices of the flow channel. A first one of the pipette devices is to aspirate the analyte fluid from a multi well plate as reservoir, and then to dispense the acquired analyte fluid into the flow channel. A second one of the pipette devices is to aspirate the liquid buffer previously filled in the flow channel. For the fluid dispenser to introduce fluid into the flow channel, pipette tips of the pipette devices are inserted in the end orifices of the flow channel. The first pipette device dispenses the analyte fluid at the same time as the second pipette device draws the liquid buffer.
A known example of the fluid dispenser includes a pipette head with a pair of the pipette devices, and a shifter for shifting the pipette head. As an example of shifter, a robot device of a perpendicular coordinate type, a multi joint type and the like can be used. It is possible for the pipette head to access an aspirating position and assay position with high precision, the aspirating position being used for drawing the analyte fluid from the multi well plate by aspiration.
To draw the analyte fluid from the multi well plate by the pipette head, only the first one of the pipette devices is inserted in the multi well plate. The second does not require using at the multi well plate. If both of the pipette devices are moved down, the second is likely to interfere with unwanted objects. Thus, the multi well plate of a normally used type cannot be used in combination. There has been an idea of use of a shifter, associated with the pipette head, for moving each pair of the pipette devices up and down
If a shifter for moving up and down each pair of the pipette devices is associated with the pipette head, the pipette head has an excessively complicated structure, and has a great size. Also, a motor must be used for each of the shifters, and will raise the manufacturing cost. Furthermore, the weight of the pipette head will be very heavy, to lower efficiency in operation due to reduction of the speed of moving the pipette head.